Allopurinol and nitric oxide activity in the cerebral circulation of those with diabetes: a randomized trial.
OBJECTIVE
Type 2 diabetes increases risk of stroke, perhaps because of impaired cerebrovascular basal nitric oxide (NO) activity. We investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol.


METHODS
We performed a randomized, double-blind, placebo-controlled crossover study. We measured the response to infusion of NG-monomethyl-L-arginine (l-NMMA) in males with type 2 diabetes before and after allopurinol or placebo. The primary end point was the change in internal carotid artery flow following L-NMMA infusion, expressed as the area under the flow-per-time curve.


RESULTS
We enrolled 14 participants. Allopurinol improved responses to L-NMMA when compared with responses associated with placebo (P = 0.032; median reduction in internal carotid artery flow following L-NMMA of 3,144 ml [95% CI 375-7,143]).


CONCLUSIONS
Xanthine oxidase inhibition with allopurinol appears to improve cerebral NO bioavailability, as evidenced by a greater response to infusion of L-NMMA.
Dawson
Jesse
J
Acute Stroke Unit, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, UK. j.dawson@clinmed.gla.ac.uk
Quinn
Terry
T
Harrow
Craig
C
Lees
Kennedy R
KR
Weir
Christopher J
CJ
Cleland
Stephen J
SJ
Walters
Matthew R
MR
D000493:Allopurinol / Q000097:blood / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D010919:Placebos; D020521:Stroke / Q000517:prevention & control; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000627:therapeutic use*
D010919:Placebos; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000493:Allopurinol